Nab-Paclitaxel and Pembrolizumab in Treating Participants with Recurrent Unresectable Locally Advanced or Metastatic Urothelial Cancer

Inclusion Criteria

• Patients with recurrent unresectable locally advanced or metastatic urothelial carcinoma (aka transitional cell carcinoma) * If unresectable locally advanced urothelial cancer, could have been previously radiated, but must have Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable, untreated progression of disease component
• Subjects may be either cisplatin-ineligible or platinum-refractory * Cisplatin ineligibility is defined as meeting at least one of the following criteria: ** Creatinine clearance (calculated or measured) < 60 mL/min (but >= 30 mL/min) calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection of creatinine for determination ** Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 audiometric hearing loss ** New York Heart Association class III/IV heart failure ** Eastern Cooperative Oncology Group (ECOG) performance status of 2 as determined by treating investigator * Platinum-refractory is defined as subjects who have progression of disease after receiving platinum-containing chemotherapy (chemotherapy could have been given in the neoadjuvant, adjuvant or metastatic setting)
• Histological or cytologically proven urothelial carcinoma; mixed urothelial/non-urothelial cell histologies are allowed but pure non-urothelial cell carcinoma is NOT allowed
• Have measurable disease based on RECIST 1.1 as determined by the investigator/radiology assessment; target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Has urothelial cancer that is not suitable for local therapy administered with curative intent if not already administered. An example of local therapy with curative intent is treatment with chemotherapy and radiation for stage 3 disease. If unresectable locally advanced urothelial cancer, could have been previously radiated, but must have progression of disease component that is untreated and RECIST 1.1 measurable
• Must have recovered (i.e., AE ≤ grade 1 or stable) from AEs due to a previously administered agent
• ECOG performance status of 0, 1 or 2
• Prior neoadjuvant or adjuvant systemic therapy or local intravesical chemotherapy or immunotherapy is permitted
• Absolute neutrophil count (ANC) >= 1500/mm3
• Hemoglobin (Hgb) >= 9 g/dL with or without packed red blood cells (pRBC) transfusion
• Platelets (Plt) >= 100,000/mm^3
• Calculated or measured creatinine clearance >= 30 mL/min) calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection of creatinine for determination
• Bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =< 2.5 x ULN
• Alanine aminotransferase (ALT) =< 2.5 x ULN
• Total Bilirubin =< 1.5 x ULN
• Women of child-bearing potential (WOCBP-defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must * Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study medication therapy (including dose interruptions), and for 6 months after last dose of study medication * Have a negative serum or urine pregnancy test (beta - human chorionic gonadotropin [hCG]) result at screening - this applies even if the subject practices true abstinence from heterosexual contact * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
• Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following study drug discontinuation, even if he has undergone a successful vasectomy * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
• Patients must have < grade 2 pre-existing peripheral neuropathy (per CTCAE)
• Be ≥ 18 years of age as of date of signing informed consent
• Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

• Prior exposure to immune-mediated therapy, including but not limited to, other anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD1, anti –PD-L1, or anti-programmed death ligand 2 (PD-L2) antibodies, including therapeutic anticancer vaccines is NOT permitted
• History of allogenic organ transplantation that requires ongoing use of immunosuppressive agents is NOT permitted
• Active or prior documented autoimmune or inflammatory disorders are NOT permitted; the following are EXCEPTIONS to this criterion and are allowed * Patients with vitiligo or alopecia, type I diabetes mellitus * Patients with hypothyroidism (e.g., following Hashimoto syndrome) * Any chronic autoimmune or inflammatory skin condition that does not require systemic therapy * Patients without active disease requiring treatment in the last 3 years may be included but only after consultation with principal investigator * Patients with celiac disease controlled by diet alone may be included but only after consultation with principal investigator
• Current or prior use of immunosuppressive medication(s) within 14 days before study treatment is NOT permitted; the following are EXCEPTIONS to this criterion and are allowed * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
• Brain metastases or spinal cord compression are NOT permitted unless they have been treated with the patient's condition being stable clinically and radiologically for at least 28 calendar days and off steroids for at least 14 calendar days prior to the start of study treatment; patients with suspected or known brain metastases at screening should have a MRI (preferred) or CT brain/head, preferably with IV contrast, to assess baseline disease status
• Active infection requiring systemic therapy including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) is NOT permitted
• Receipt of live attenuated vaccine within 28 calendar days prior to the first study treatment is NOT permitted
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 28 calendar days of the first dose of treatment
• CTCAE grade >= 2 peripheral neuropathy is NOT permitted
• If subjects received major surgery they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting trial therapy
• Has a known additional malignancy that is progressing or requires active treatment
• Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to nab-paclitaxel or anti-PD1/PDL1 or human albumin
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial; at the time of signing informed consent is a known regular user (including "recreational use") of any illicit drug(s) or had a recent history (within the last year) of drug or alcohol abuse
• Pregnancies * Females: nab-paclitaxel can cause harm to an unborn child if given to a pregnant woman; females may not take part in this study if pregnant or breast-feeding for 6 months after last dose of study drug; because of the possible risks to an unborn child, women of child-bearing potential (WOBCP) will be asked to take a pregnancy test prior to starting study medication * Males: Male subjects should avoid fathering a child while receiving study medication and for 6 months after the last dose of study medication; males must agree to complete abstinence from heterosexual contact or use a condom during sexual contact with a female of child bearing potential while receiving study medication and within 6 months after last dose of study medication; if a female partner of a male subject taking investigational product becomes pregnant, the male subject taking the product should notify the principal investigator, and the pregnant female partner should be advised to call their healthcare provider immediately * Subjects (both males and female) should practice effective contraception during study and for 6 months after the last dose of study medication
• Patients with biliary obstruction or biliary stent are excluded
• Patients with a history of prior thoracic radiation > 30 gray (Gy)